Critical Involvement of CD44 in T Helper Type 2 Cell-Mediated Eosinophilic Airway Inflammation in a Mouse Model of Acute Asthma.

Shigeki Katoh

doi:10.3389/fimmu.2021.811600

Abstract

Interactions between CD44 and hyaluronan (HA) are crucial for recruiting leukocytes to inflamed tissues. This review summarizes findings from our studies of the roles of CD44-HA interactions in leukocyte trafficking, with a particular focus on airway T helper type 2 (Th2) cells in mouse models of acute asthma. In a mite allergen-induced model of acute asthma, intraperitoneal injection of anti-CD44 monoclonal antibodies blocked lymphocytes and eosinophils from accumulating in the lung, and suppressed both the antigen-induced increase in Th2 cytokines in the bronchoalveolar lavage fluid (BALF) and airway hyperresponsiveness (AHR). CD44 deficiency was associated with decreased mite allergen-induced Th2 cell-mediated airway inflammation and AHR in sensitized mice. Asthmatic responses to antigen-sensitized splenic CD4+ T cells transferred from CD44-deficient mice were weaker than in wild-type mice. Administration of anti-CD44 monoclonal antibodies preferentially suppressed the airway accumulation of antigen-specific Th2 cells induced by antigen challenge, without affecting Th1 and Th17 cells. Increased HA-binding ability of CD44 and expression of Neu1 sialidase were observed on antigen-specific Th2 cells compared with antigen-specific Th1 and Th17 cells. Finally, in a mouse model of acute asthma, neuraminidase 1-deficient SM/J mice exhibited a lower Th2 cytokine concentration and a lower absolute Th2 cell number in the BALF, as well as an attenuated AHR. Our findings indicate that CD44 critically contributes to the antigen challenge-induced airway accumulation of antigen-specific Th2 cells, without affecting Th1 and Th17 cells, in mice. Furthermore, neuraminidase 1 activity is necessary for the interaction between HA and CD44, and Th2 cell-mediated airway inflammation.

Highlights

The cell surface adhesion receptor cluster of differentiation 44 (CD44) is a heavily glycosylated molecule that regulates the adhesion of lymphocytes to inflamed endothelial cells, T cell activation, tumor metastasis, and many other cellular processes
We studied the contribution of CD44 expressed on CD4+ T cells to the airway accumulation of Th2 cells using CD44-deficient mice and anti-CD44 monoclonal antibodies (mAbs)
Anti-CD44 mAbs preferentially suppressed the antigen challenge-induced accumulation of these Th2 cells in the airway, as compared with Th1 and Th17 cells in a mouse Th cell-transfer model [24, 25]. These findings demonstrated that CD44-expressing CD4+ T cells are critical for the airway accumulation of antigen-specific Th2 cells, but not Th1 or Th17 cells (Figure 1)

Summary

Introduction

The cell surface adhesion receptor cluster of differentiation 44 (CD44) is a heavily glycosylated molecule that regulates the adhesion of lymphocytes to inflamed endothelial cells, T cell activation, tumor metastasis, and many other cellular processes. We investigated how CD44 participates in the airway accumulation of CD4+ T cells by developing an asthmatic phenotype in a mouse model of allergic acute asthma. ROLE OF CD44 IN ALLERGEN-INDUCED ACUTE AIRWAY INFLAMMATION IN MICE

Results

Conclusion